6-(2,6-二氯苯基)-2-[[4-[2-(二乙基氨基)乙氧基]苯基]氨基]-8-甲基吡啶并[2,3-D]嘧啶-7(8H)-酮盐酸盐
生物活性靶点体外研究体内研究
中文名称 | 6-(2,6-二氯苯基)-2-[[4-[2-(二乙基氨基)乙氧基]苯基]氨基]-8-甲基吡啶并[2,3-D]嘧啶-7(8H)-酮盐酸盐 |
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中文同义词 | 6-(2,6-二氯苯基)-2-[[4-[2-(二乙基氨基)乙氧基]苯基]氨基]-8-甲基吡啶并[2,3-D]嘧啶-7(8H)-酮盐酸盐;PD 166285 双盐酸盐;化合物 PD0166285 DIHYDROCHLORIDE |
英文名称 | PD 166285 |
英文同义词 | 6-(2,6-Dichlorophenyl)-2-[[4-[2-(diethylamino)ethoxy]phenyl]amino]-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one Hydrochloride;PD 166285;PD 166285 - CAS 212391-63-4 - Calbiochem;6-(2,6-dichlorophenyl)-2-[4-[2-(diethylamino)ethoxy]anilino]-8-methylpyrido[2,3-d]pyrimidin-7-one,dihydrochloride;6-(2,6-Dichlorophenyl)-2-[[4-[2-(diethylamino)ethoxy]phenyl]amino]-8-methylpyrido[2,3-d]pyrimidin-7(8H)-onedihydrochloride;PD 166285 dihydrochloride;6-(2,6-Dichloro-phenyl)-2-[4-(2-diethylaMino-ethoxy)-phenylaMino]-8-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one hydrochloride;6-(2,6-Dichlorophenyl)-2-[[4-[2-(diethylamino)ethoxy]phenyl]amino]-8-methylpyrido[2,3-d]pyrimi |
CAS号 | 212391-63-4 |
分子式 | C26H29Cl4N5O2 |
分子量 | 585.37 |
EINECS号 | |
相关类别 | Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Protein Kinase Inhibitors and Activators |
Mol文件 | 212391-63-4.mol |
结构式 |
6-(2,6-二氯苯基)-2-[[4-[2-(二乙基氨基)乙氧基]苯基]氨基]-8-甲基吡啶并[2,3-D]嘧啶-7(8H)-酮盐酸盐 性质
熔点 | 239-242?C |
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储存条件 | Desiccate at RT |
溶解度 | 可溶于二甲基亚砜、甲醇 |
形态 | 淡黄色固体 |
颜色 | 粘黄色 |
稳定性 | 吸湿性 |
6-(2,6-二氯苯基)-2-[[4-[2-(二乙基氨基)乙氧基]苯基]氨基]-8-甲基吡啶并[2,3-D]嘧啶-7(8H)-酮盐酸盐 用途与合成方法
生物活性
PD0166285 dihydrochloride是 P-gp 的一个底物,是 WEE1 抑制剂,也可微弱抑制 Myt1,IC50 值分别为 24 和 72 nM。PD0166285 dihydrochloride 对 Chk1 的 IC50 值为3.433 μM。
靶点
IC50: 24 nM (WEE1), 72 nM (Myt1), 3.433 μM (Chk1).
体外研究
PD0166285 (0.5 μM) dramatically inhibits irradiation-induced Cdc2 phosphorylation at the Tyr-15 and Thr-14 in seven of seven cancer cell lines.
PD0166285 sensitizes radiation-induced cell killing in p53 mutant HT29 cells and in the E6-transfected, p53-null ovarian cancer cell line PA-1 but to a lesser extent in p53 wild-type PA-1 cells. PD0166285 abrogates irradiation-induced G2 arrest and significantly increases mitotic cell populations.
PD0166285 acts as a radiosensitizer to sensitize cells to radiation-induced cell death with a sensitivity enhancement ratio of 1.23.
Western Blot Analysis
Cell Line: | Human and mouse cancer cell lines (HCT116, HT29, DLD-1, HCT8, H460, HeLa, C 26). |
Concentration: | 0.5 μM. |
Incubation Time: | 4 h. |
Result: | Inhibited Cdc2Y15 and CdcT14 phosphorylation. |
体内研究
Animal Model: | Wild-type, Abcg2 -/- , Abcb1a/b -/- and Abcb1a/b;Abcg2 -/- FVB mice. |
Dosage: | 5 mg/kg. |
Administration: | IV. |
Result: | C max is about 400 ng/mL. P-gp, but not BCRP, limited the brain penetration of PD0166285. |